Diltiazem hydrochloride is a calcium ion influx inhibitor which is commercially utilized in the treatment of angina pectoris due to coronary artery spasm and chronic stable angina.
Controlled delivery devices for therapeutically active agents are well known in the art. Generally, these devices may be characterized as either diffusion controlled delivery systems or osmotic dispensing devices. U.S. Pat. No. 3,538,214 discloses a diffusion controlled device in which a tablet core containing an active ingredient is surrounded by a water insoluble coating which contains film modifying agent soluble in the external fluids in the gastrointestinal tract. An example of an osmotic device is described in U.S. Pat. Nos. 3,845,770 and 3,916,899 which is a core composition of an active agent and an osmotically effective solute which is enclosed by an insoluble semipermeable wall having a release means. Numerous modifications to these types of delivery devices have been described in the art in an effort to improve their release characteristics.
The use of pore formers in substantially water impermeable polymers, such as polyvinyl chloride, is disclosed in J. Pharm. Sci. 72, 772-775 and U.S. Pat. No. 4,244,941. The devices release the core contents by simple diffusion through the pores in the coating.
U.S. Pat. No. 3,957,523 discloses a device which has pH sensitive pore formers in the wall.
U.S. Pat. Nos. 4,256,108; 4,160,452; 4,200,098 and 4,285,987 disclose devices with pore formers in only one of at least two wall layers. These devices contain a drilled hole for the release of the core contents.
Co-pending U.S. Pat. applications Ser. Nos. 073781 and 073596 disclose systems which comprise an inner core compartment of osmotically active composition surrounded by an enclosing controlled porosity wall material that is substantially permeable to both solute and external fluid. These systems are osmotic dispensing devices for a broad range of therapeutically active agents. However, the delivery of a highly soluble agent from these devices at a constant rate is difficult to achieve.
U.S. Pat. No. 4,326,525 addresses the problem of delivering an active agent from an osmotic device by incorporating into the core a buffer which enters into a proton transfer or neutralization reaction with the agent thereby producing an aqueous soluble agent salt within the device.